Development of new cancer therapy strategies by promoting aberrant cell division in the presence of replication inhibitors

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K18423
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KAKUSHO Naoko 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (30599593)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Cdc7キナーゼ / Wee1キナーゼ / 細胞周期 / S期 / M期 / がん細胞死 / キナーゼ阻害剤 / DNA複製

Outline of Final Research Achievements

On the basis of our proposal that inhibition of S phase causes cancer cells to proceed into lethal M phase in the presence of unreplicated genomic segment, we proposed a novel cancer therapy strategy in which cancer cell death is promoted by combination of S phase inhibition and M phase promotion. We used inhibitors of Cdc7 kinase, essential for firing of replication origins in S phases, and showed that the Cdc7 inhibitor causes cell death only after cells have progressed through S phase in the presence of the inhibitor, apparently causing cancer cells to enter aberrant M phase. When combined with MK1775, the inhibitor of Wee1 kinase that inhibits M phase, Cdc7 inhibitor caused synergistic cell death effect on cancer cells including Colo205 (colon cancer) and CCRF-CEM(leukemia). HU and Aphidicolin also induced efficient cancer cell death in combination with MK1775.

Free Research Field

分子生物学、細胞生物学